Abstract
Dynamic positron emission tomography (PET) imaging of with L-[methyl- 11 C]methionine (11C-MET) was developed in the late 1990’s to non-invasively estimate skeletal muscle protein synthesis, but no studies have shown that the measurements respond to resistance exercise, which stimulates protein synthesis in humans. Ten healthy women aged 25-75 years underwent a 14-hour fast, followed by unilateral knee extension and flexion exercise and consumption of an 8-ounce serving of fruit juice. Five subjects underwent dynamic 11C-MET PET imaging of the mid-thigh 2-3 hours after exercise and five were imaged 1 hour after exercise. Images were processed to obtain the Patlak slope K i , which describes the fractional extraction rate of 11C-MET into skeletal muscle protein. Additionally, the images were processed with a three-compartment kinetic model to determine rate constants for 11C-MET transport between muscle tissue, protein and plasma. All subjects showed excellent mid-thigh uptake of 11C-MET. Subjects imaged 2-3 hours after exercise showed no unilateral enhancement. However, subjects imaged one hour post-exercise showed an enhancement of 11C-MET uptake in the exercised leg compared to the control leg, corresponding to K i elevations between 3.8% - 31.1%. From the three-compartment analysis, the increased uptake corresponded primarily to an increased rate constant for extraction of 11C-MET from plasma to skeletal muscle tissue. Finally, older subjects tended to have smaller values of K i than the younger subjects. In summary, 11C-MET kinetics is responsive to a unilateral exercise stimulus, and this technique may prove useful to study skeletal muscle amino acid kinetics in response to exercise, aging and other conditions
Highlights
Aging is characterized by loss of skeletal muscle mass and an even larger deterioration of muscle strength [1]
The Patlak slope Ki, a quantitative measure of extraction of the substrate from plasma to the bound compartment in muscle, agreed with the Ki calculated from the kinetic parameter estimates from Fischman et al [9]
The Ki derived from the control legs of our five subjects imaged at 2-3 hours post exercise, which represented the closest equivalent in our data to resting state measures, had a mean value of 0.0108 cm3/ min/g compared to 0.013cm3/min/g for the 6 subjects imaged in the earlier work [9]
Summary
Aging is characterized by loss of skeletal muscle mass and an even larger deterioration of muscle strength [1]. These changes are associated with impaired performance and mobility, and increased risk of falls and injuries, among the growing elderly population [2,3,4,5]. Age-related muscle atrophy results in good part from disruption in the normal function of skeletal muscle tissue, which involves a dynamic balance between synthesis of muscle protein from amino acids in the cellular milieu and dissociation of protein into free amino acids [6]. Measurements of protein synthesis rates are an important tool for investigating the effect of aging on skeletal muscle, and for understanding variations in the anabolic response of muscle tissue to exercise and other interventions
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